The beneficial health effects of phenolic compounds isolated from Olea Europea are now evident. In particular, the antioxidant and anti-inflammatory properties of hydroxytyrosol have been widely investigated and shown to have beneficial uses as an antioxidant for the treatment of oxygen free radical-associated diseases or conditions. Specifically, United States Patent Pub. No. US 2011/0034519 A1 describes compositions for and methods of administration of hydroxytyrosol, and optionally other dietary supplements, to a subject in need thereof for the inhibition and treatment of necrosis and extended quiescence that result in cellular necrosis instead of normal proliferation, which is incorporated herein by reference in its entirety. In addition, the beneficial properties of hydroxytyrosol for reversing damage to cells, promoting wound healing, and inhibiting necrosis have been similarly demonstrated. Specifically, United States Patent Pub. No. US 2013-0266545 A1 describes compositions and methods for reversing damage to skin cells and, in particular, to compositions and methods for wound healing and inhibiting necrosis, for example, in the treatment of skin that is distressed or wounded as result of a disease or other biological condition or process.
Compounds for treatment of diseases are often non-naturally occurring, cause harmful side-effects, and are expensive to produce. Chemotherapeutic agents for the treatment of cancer can be prohibitively expensive, and cause a variety of serious side effects. It is therefore unexpected and desirable that the co-therapy and/or co-administration of regimens comprising hydroxytyrosol and chemotherapeutic agents demonstrate beneficial results in treating malignancy.
Furthermore, oxidants and free radical species, such as reactive oxygen species (ROS), are known to contribute to cell damage and/or cell death, as well as having a role in various metabolic and immune system processes. Synthetic antioxidants such as butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) and tertiary butylhydroquinone (TBHQ) have demonstrated carcinogenicity and other toxic properties, underscoring the need for natural antioxidants. Growing evidence links antioxidants with a decreased risk of chronic diseases such as coronary heart disease, cancer, and several other aging-related health concerns (Tahseen Iqbal et al., Antioxidant Activity and Volatile and Phenolic Profiles of Essential Oil and Different Extracts of Wild Mint (Mentha longifolia) from the Pakistani Flora, Journal of Analytical Methods in Chemistry, (2013) vol. 2013, Article ID 536490). Oxidative stress has been linked to collateral damage in cancer chemotherapy. (See, e.g., Yumin Chen et al., Collateral Damage in Cancer Chemotherapy: Oxidative Stress in Nontargeted Tissues (2007) Mol. Interventions 7(3); 147-156). Antioxidant activity has also been linked to wound healing. (See, e.g., Arti Shukla et al. Asiaticoside-induced Elevation of Antioxidant Levels in Healing Wounds (1999) Phytother. Res. 13, 50-54); to induction of angiogenesis (see Elena Daghini et al., Antioxidant vitamins induce angiogenesis in the normal pig kidney (2007) American Journal of Physiology—Renal Physiology. 293; F371-F381); and high-glucose induced dysfunction (see G. Cohen et al., The roles of hyperglycaemia and oxidative stress in the rise and collapse of the natural protective mechanism against vascular endothelial cell dysfunction in diabetes (2007), 113(4-5); 259-267). Reduction in the concentration of one or more radical species in a biological environment thus has benefits in various biological environments for amelioration of a host of conditions. As a result compounds capable of enhancing the antioxidant capability in cells, animals, or individuals are important tools in treating or preventing a wide range of conditions. The expression of lysine specific demethylase 1 (LSD1) in various cancers is prevalent and represents a potential mechanism for prevention, treatment and/or detection of cancers. Conventional efforts to develop specific inhibitors of the LDS1 protein expressed in a majority of cancers have had limited success to date. In particular, development of specific inhibitors of the LDS1 protein active and binding sites has not resulted in significant advances in cancer treatment and/or prevention. However, the inhibition of LSD1 activity by hydroxytyrosol, hydroxytyrosol derivatives, substituted hydroxytyrosol compounds and/or hydroxytyrosol prodrugs has provided surprising and unexpected results, demonstrating at least equivalent LSD1 inhibition (or superior inhibition) to known LSDI inhibitors.
Accordingly, it is an objective of the claimed invention to provide compositions and methods for the treatment of diseases currently treated with chemotherapeutic agents, including cancers, malignancies, and tumors.
A further object of the invention is to provide compositions and methods for inhibiting LSD1 activity, particularly in cancer cells, malignancies, and tumors.
A further object of the invention is to provide methods and compositions to increase the antioxidant capacity of normal cells.
Other objects, advantages and features of the present invention will become apparent from the following specification taken in conjunction with the accompanying drawings.